Cognitive Assessment in Neuromyelitis Optica Spectrum Disorders: A Systematic Review and Meta-Analysis
Rebeca Silva1, Filipi Andreão2, Karlos Daniell dos Santos3, Lucas Nascimento4, Leandro Lessa5, Helvécio Filho6, Lorenzo Anselmi Anselmi7, Diogo Haddad Santos8
1Federal University of Paraíba, Brazil, 2Federal University of Rio de Janeiro, Brazil, 3Federal University of Roraima, Brazil, 4University of Brasília, Brazil, 5Pontifical Catholic University of Paraná, 6University of Fortaleza, Brazil, 7Faculty Mackenzie Evangelical, Brazil, 8Moema, Hospital Alemão Oswaldo Cruz, Brazil
Objective:

To evaluate the cognitive impairments associated with neuromyelitis optica spectrum disorders (NMOSD) through a systematic review and meta-analysis of studies assessing cognitive function using various neuropsychological tests.

Background:

NMOSD is a chronic, autoimmune disease affecting the central nervous system, with cognitive dysfunction reported in 29-67% of patients. Despite the prevalence of cognitive deficits in NMOSD, standardization in cognitive testing remains limited. This review aims to summarize the cognitive domains affected in NMOSD and assess the accuracy of neurocognitive tests employed in evaluating these patients.

Design/Methods:
A systematic search of PubMed, Embase, and Cochrane databases identified 232 articles, of which 28 studies met inclusion criteria, encompassing 1,365 NMOSD patients. Cognitive assessments were evaluated using multiple scales, including the Beck Depression Inventory-II (BDI-II), Controlled Oral Word Association Test (COWAT), California Verbal Learning Test (CVLT), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities Test (SDMT). Heterogeneity was assessed using I² statistics, and sensitivity analyses were conducted to explore the impact of outlier studies.
Results:
All cognitive scales demonstrated high heterogeneity (I² > 50%), with values ranging from 82% to 100%. Random-effects models were applied due to significant variability across studies. Cognitive impairments were observed across multiple domains, including memory (CVLT: 26.02 [95% CI 13.18 to 51.39]), executive function (COWAT: 24.40 [95% CI 16.22 to 36.22]), attention (PASAT: 33.41 [95% CI 27.19 to 41.04]), and processing speed (SDMT: 41.00 [95% CI 34.84 to 48.26]). Sensitivity analysis identified one outlier in MMSE data, reducing heterogeneity (I² = 19%) when omitted.
Conclusions:
Cognitive dysfunction is prevalent in NMOSD patients, impacting several domains. However, significant heterogeneity across studies indicates a lack of standardized cognitive testing. Future research should aim to validate specific neuropsychological assessments for NMOSD to improve diagnostic accuracy and patient management.
10.1212/WNL.0000000000212620
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